The Effect of Tomatine on Gene Expression and Cell Monolayer Integrity in Caco-2

More understanding of the risk-benefit effect of the glycoalkaloid tomatine is required to be able to estimate the role it might play in our diet. In this work, we focused on effects towards intestinal epithelial cells based on a Caco-2 model in order to analyze the influence on the cell monolayer i...

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Published in:Molecules (Basel, Switzerland) Switzerland), 2018-03, Vol.23 (3), p.644
Main Authors: Arena, Mattia P, Govers, Coen, Lotti, Concetta, Ricciardi, Luigi, Wichers, Harry J, Mes, Jurriaan J
Format: Article
Language:English
Subjects:
Apoptosis
Bioavailability
Biocompatibility
Biological activity
Biosynthesis
Caco-2 Cells
Cell cycle
Cell Cycle - drug effects
Cell Proliferation - drug effects
Cell Survival - drug effects
Cholesterol
Consumer Science & Health
Cytokines
Epithelial cells
Epithelial Cells - cytology
Epithelial Cells - drug effects
FBR Consumer Science & Health
Food matrix
Food, Health & Consumer Research
Gene expression
Gene Expression Profiling - methods
Gene Expression Regulation - drug effects
Gene Regulatory Networks - drug effects
Glucose metabolism
glycoalkaloid
gut
Humans
immune system
Interleukin 1
Interleukin 8
Intestine
Intestines - cytology
Intestines - drug effects
Lipid metabolism
Lipid Metabolism - drug effects
Metabolism
Models, Biological
Molecular Structure
Monolayers
Proliferating cell nuclear antigen
qPCR
Receptors, LDL - genetics
Thymic stromal lymphopoietin
Tight junctions
Tight Junctions - genetics
Tomatine
Tomatine - chemistry
Tomatine - pharmacology
Tomatoes
Toxicity
Tumor necrosis factor-α
Viability
VLAG
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Mes, Jurriaan J
description More understanding of the risk-benefit effect of the glycoalkaloid tomatine is required to be able to estimate the role it might play in our diet. In this work, we focused on effects towards intestinal epithelial cells based on a Caco-2 model in order to analyze the influence on the cell monolayer integrity and on the expression levels of genes involved in cholesterol/sterol biosynthesis (LDLR), lipid metabolism (NR2F2), glucose and amino acid uptake (SGLT1, PAT1), cell cycle (PCNA, CDKN1A), apoptosis (CASP-3, BMF, KLF6), tight junctions (CLDN4, OCLN2) and cytokine-mediated signaling (IL-8, IL1β, TSLP, TNF-α). Furthermore, since the bioactivity of the compound might vary in the presence of a food matrix and following digestion, the influence of both pure tomatine and in vitro digested tomatine with and without tomato fruit matrix was studied. The obtained results suggested that concentrations
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In this work, we focused on effects towards intestinal epithelial cells based on a Caco-2 model in order to analyze the influence on the cell monolayer integrity and on the expression levels of genes involved in cholesterol/sterol biosynthesis (LDLR), lipid metabolism (NR2F2), glucose and amino acid uptake (SGLT1, PAT1), cell cycle (PCNA, CDKN1A), apoptosis (CASP-3, BMF, KLF6), tight junctions (CLDN4, OCLN2) and cytokine-mediated signaling (IL-8, IL1β, TSLP, TNF-α). Furthermore, since the bioactivity of the compound might vary in the presence of a food matrix and following digestion, the influence of both pure tomatine and in vitro digested tomatine with and without tomato fruit matrix was studied. The obtained results suggested that concentrations &lt;20 µg/mL of tomatine, either undigested or in vitro digested, do not compromise the viability of Caco-2 cells and stimulate cytokine expression. This effect of tomatine, in vitro digested tomatine or in vitro digested tomatine with tomato matrix differs slightly, probably due to variations of bioactivity or bioavailability of the tomatine. The results lead to the hypothesis that tomatine acts as hormetic compound that can induce beneficial or risk toxic effects whether used in low or high dose.</description><identifier>ISSN: 1420-3049</identifier><identifier>EISSN: 1420-3049</identifier><identifier>DOI: 10.3390/molecules23030644</identifier><identifier>PMID: 29533987</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Apoptosis ; Bioavailability ; Biocompatibility ; Biological activity ; Biosynthesis ; Caco-2 Cells ; Cell cycle ; Cell Cycle - drug effects ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Cholesterol ; Consumer Science &amp; Health ; Cytokines ; Epithelial cells ; Epithelial Cells - cytology ; Epithelial Cells - drug effects ; FBR Consumer Science &amp; Health ; Food matrix ; Food, Health &amp; Consumer Research ; Gene expression ; Gene Expression Profiling - methods ; Gene Expression Regulation - drug effects ; Gene Regulatory Networks - drug effects ; Glucose metabolism ; glycoalkaloid ; gut ; Humans ; immune system ; Interleukin 1 ; Interleukin 8 ; Intestine ; Intestines - cytology ; Intestines - drug effects ; Lipid metabolism ; Lipid Metabolism - drug effects ; Metabolism ; Models, Biological ; Molecular Structure ; Monolayers ; Proliferating cell nuclear antigen ; qPCR ; Receptors, LDL - genetics ; Thymic stromal lymphopoietin ; Tight junctions ; Tight Junctions - genetics ; Tomatine ; Tomatine - chemistry ; Tomatine - pharmacology ; Tomatoes ; Toxicity ; Tumor necrosis factor-α ; Viability ; VLAG</subject><ispartof>Molecules (Basel, Switzerland), 2018-03, Vol.23 (3), p.644</ispartof><rights>2018. 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In this work, we focused on effects towards intestinal epithelial cells based on a Caco-2 model in order to analyze the influence on the cell monolayer integrity and on the expression levels of genes involved in cholesterol/sterol biosynthesis (LDLR), lipid metabolism (NR2F2), glucose and amino acid uptake (SGLT1, PAT1), cell cycle (PCNA, CDKN1A), apoptosis (CASP-3, BMF, KLF6), tight junctions (CLDN4, OCLN2) and cytokine-mediated signaling (IL-8, IL1β, TSLP, TNF-α). Furthermore, since the bioactivity of the compound might vary in the presence of a food matrix and following digestion, the influence of both pure tomatine and in vitro digested tomatine with and without tomato fruit matrix was studied. The obtained results suggested that concentrations &lt;20 µg/mL of tomatine, either undigested or in vitro digested, do not compromise the viability of Caco-2 cells and stimulate cytokine expression. This effect of tomatine, in vitro digested tomatine or in vitro digested tomatine with tomato matrix differs slightly, probably due to variations of bioactivity or bioavailability of the tomatine. 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Govers, Coen ; Lotti, Concetta ; Ricciardi, Luigi ; Wichers, Harry J ; Mes, Jurriaan J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c544t-876e498cf638f94f495c23442abadd1cc0f36bb800d8d8dc8039f9fba15912f13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Apoptosis</topic><topic>Bioavailability</topic><topic>Biocompatibility</topic><topic>Biological activity</topic><topic>Biosynthesis</topic><topic>Caco-2 Cells</topic><topic>Cell cycle</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Cell Survival - drug effects</topic><topic>Cholesterol</topic><topic>Consumer Science &amp; Health</topic><topic>Cytokines</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - cytology</topic><topic>Epithelial Cells - drug effects</topic><topic>FBR Consumer Science &amp; Health</topic><topic>Food matrix</topic><topic>Food, Health &amp; Consumer Research</topic><topic>Gene expression</topic><topic>Gene Expression Profiling - methods</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Gene Regulatory Networks - drug effects</topic><topic>Glucose metabolism</topic><topic>glycoalkaloid</topic><topic>gut</topic><topic>Humans</topic><topic>immune system</topic><topic>Interleukin 1</topic><topic>Interleukin 8</topic><topic>Intestine</topic><topic>Intestines - cytology</topic><topic>Intestines - drug effects</topic><topic>Lipid metabolism</topic><topic>Lipid Metabolism - drug effects</topic><topic>Metabolism</topic><topic>Models, Biological</topic><topic>Molecular Structure</topic><topic>Monolayers</topic><topic>Proliferating cell nuclear antigen</topic><topic>qPCR</topic><topic>Receptors, LDL - genetics</topic><topic>Thymic stromal lymphopoietin</topic><topic>Tight junctions</topic><topic>Tight Junctions - genetics</topic><topic>Tomatine</topic><topic>Tomatine - chemistry</topic><topic>Tomatine - pharmacology</topic><topic>Tomatoes</topic><topic>Toxicity</topic><topic>Tumor necrosis factor-α</topic><topic>Viability</topic><topic>VLAG</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Arena, Mattia P</creatorcontrib><creatorcontrib>Govers, Coen</creatorcontrib><creatorcontrib>Lotti, Concetta</creatorcontrib><creatorcontrib>Ricciardi, Luigi</creatorcontrib><creatorcontrib>Wichers, Harry J</creatorcontrib><creatorcontrib>Mes, Jurriaan J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health Medical collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Databases</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health &amp; 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This effect of tomatine, in vitro digested tomatine or in vitro digested tomatine with tomato matrix differs slightly, probably due to variations of bioactivity or bioavailability of the tomatine. The results lead to the hypothesis that tomatine acts as hormetic compound that can induce beneficial or risk toxic effects whether used in low or high dose.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>29533987</pmid><doi>10.3390/molecules23030644</doi><orcidid>https://orcid.org/0000-0002-0627-6214</orcidid><oa>free_for_read</oa></addata></record>
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subjects Apoptosis
Bioavailability
Biocompatibility
Biological activity
Biosynthesis
Caco-2 Cells
Cell cycle
Cell Cycle - drug effects
Cell Proliferation - drug effects
Cell Survival - drug effects
Cholesterol
Consumer Science & Health
Cytokines
Epithelial cells
Epithelial Cells - cytology
Epithelial Cells - drug effects
FBR Consumer Science & Health
Food matrix
Food, Health & Consumer Research
Gene expression
Gene Expression Profiling - methods
Gene Expression Regulation - drug effects
Gene Regulatory Networks - drug effects
Glucose metabolism
glycoalkaloid
gut
Humans
immune system
Interleukin 1
Interleukin 8
Intestine
Intestines - cytology
Intestines - drug effects
Lipid metabolism
Lipid Metabolism - drug effects
Metabolism
Models, Biological
Molecular Structure
Monolayers
Proliferating cell nuclear antigen
qPCR
Receptors, LDL - genetics
Thymic stromal lymphopoietin
Tight junctions
Tight Junctions - genetics
Tomatine
Tomatine - chemistry
Tomatine - pharmacology
Tomatoes
Toxicity
Tumor necrosis factor-α
Viability
VLAG
title The Effect of Tomatine on Gene Expression and Cell Monolayer Integrity in Caco-2
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